Project Summary The increasing incidence of diabetes in the US population and the inertial wave of aging in Americans will ensure that diabetic retinopathy (DR) remains one of the principal threats to the sight of adult patients and a significant management challenge for the clinical community. It is now clear that the peripheral retina is the site of pathology in many vision-threatening eye diseases, including DR. Evaluation of the retinal periphery, therefore, is important for screening, diagnosis, monitoring, and treatment of disease manifestations. Historically, imaging of the peripheral retina has been limited and difficult to obtain; recent advancements in wide-field photography, however, have dramatically improved the ability to image the anterior retina. To reveal vascular involvements in the peripheral retina, invasive imaging techniques, e.g., fluorescein angiography (FA) and indo-cyanine green angiography (ICGA), are currently used. Both techniques have traditionally been utilized to make diagnoses and treatment decisions, but they only provide two-dimensional (2D) images and require intravascular injections that risk complications. It would be highly advantageous to be capable of 3D visualization of peripheral vascular perfusion with capillary-level resolution, both to reveal the detailed functional architecture of the microvascular network and to permit quantification of the perfusion status of the retina. This information would be fundamental to better understanding of retinal diseases that has peripheral vascular involvements, e.g. DR, resulting in more informed and targeted treatment decisions. In this project, we propose to develop a clinically applicable 3D ultra widefield optical microangiography (UW-OMAG) system capable of imaging the neural retina at ~180-degree field of view. We envision that this novel, non-invasive, and label-free optical imaging method will quantify the morphology of blood vessels and permit assessment of their spatial relations in 3D, not only in the central macular region, but in the peripheral retina. Concurrently, total retinal blood flow (RBF) and vascular volumes of the retina can be quantitatively assessed. To achieve this goal, we will first design and construct a novel, UW-OMAG system based on swept source optical coherence tomography capable of 400 kHz A-scan rate. The focus will be on solving challenges associated with creating an UW-OMAG retinal imaging system that is capable of providing an imaging range of >12mm with minimal system sensitivity roll-off characteristics so that it is able to adapt and image the curved posterior segment, and achieving an unprecedented imaging field of view ~180o. We will then utilize this clinically applicable prototype to validate its accuracy for visualizing the peripheral retinal microvasculature, compared to ultra widefield fundus photography and FA. Finally, we will perform UW-OMAG pilot imaging studies in 160 subjects of normal and DR subjects to demonstrate clinical feasibility and usefulness of this new label-free 3D ultra widefield microangiography of vascular structure and function. This study will serve as the foundation for next generation of OCT angiography and for interpretation of UW-OMAG data in future.